Novel Technique Allows for Discovery of Unknown Viruses

A chance discovery has opened up a new method of finding unknown viruses. Oxford University researchers have revealed that Next-Generation Sequencing (NGS) technology and its associated online DNA databases can be used to discover unknown viruses. They have developed algorithms that detect DNA from viruses in fish blood or tissue samples and could be used to identify viruses in a range of different species.

The team published its findings (“A Novel Viral Lineage Distantly Related to Herpesviruses Discovered within Fish Genome Sequence Data”) in Virus Evolution.

“In this study, we demonstrate the utility of combining evolutionary approaches with bioinformatics to mine non-viral genome data for viruses, by adapting methods from paleovirology. We report the discovery of a new lineage of dsDNA [double-stranded DNA] viruses that are associated with at least fifteen different species of fish,” write the investigators. “The identification of novel viruses from genome data shows that our approach has applications in genomics, virology, and the development of best practices for aquaculture and farming.”

Aris Katzourakis, Ph.D., and Amr Aswad, Ph.D., research associates in the department of zoology, made their discovery by chance. They were searching for an ancient herpesvirus in primates and found evidence of two new undocumented viruses.

In a different experiment to find new fish-infecting herpesviruses, they used the technique to examine more than 50 fish genomes for recognizable viral DNA. They not only found the expected herpesviruses but they also identified unusual viruses that may even be a new viral family. The traits were found scattered in fragments of 15 different species of fish, including the Atlantic salmon and rainbow trout.

“In the salmon genome, we found what seems to be a complete and independent viral genome, as well as dozens of fragments of viral DNA that had integrated into the fish DNA,” said Dr. Katzourakis. “We know from recent studies that viruses are able to integrate into the genome of their host, sometimes remaining there for millions of years. In this case, it looks like the virus may have acquired the ability to integrate by stealing a gene from the salmon itself, which explains how it has become so widespread in the salmon genome.”

“Discovering new viruses has historically been biased toward people and animals that exhibit symptoms of disease,” noted Dr. Aswad, co-author of the paper. “But, our research shows how useful next-generation DNA sequencing can be in viral identification. To many, viral DNA in, say, chimp or falcon data is a nuisance and a rogue contaminant that needs to be filtered from results. But we consider these an opportunity waiting to be exploited, as they could include novel viruses that are worth studying—as we have found in our research. We could be throwing away very valuable data.”

The team believes its methodology has applications in the identification of viruses in other species, especially those known to harbor transmissible disease. Bats and rodents, for example, carry infectious diseases to which they seem to be immune. Insects such as mosquitoes are also carriers of viral diseases that harm humans, such as Zika. If applied effectively the method could uncover other viruses before an outbreak even happens.

“One of the real strengths of this technique, as compared to more traditional virology approaches, is the speed of discovery, and the lack of reliance on identifying a diseased individual,” added Dr. Katzourakis. “The viral data collected that may otherwise be discarded as a nuisance, is a unique resource for looking for both pathogenic and benign viruses that would otherwise have remained undiscovered.”

The researchers will now try to determine the impact of the viruses and whether they have any long-term implications for disease or commercial fish farming. While an infectious virus may not cause disease in its natural host, there is a risk of cross-species transmission to either farmed fish or wild populations.